The Joint Center for Structural Genomics (JCSG) aims to participate in the NIGMS PSI:Biology program as a Center for High-Throughput Structure Determination. The JCSG high-throughput (HT) platform assembled over the past ten years will efficiently deliver large numbers of protein structures to the community by both x-ray crystallography and NMR on a wide range of targets from bacteria to human, including challenging targets such as eukaryotic proteins, protein-protein and other macromolecular complexes. Throughout PSI:Biology, the JCSG will adapt and tailor its operations to achieve the programmatic goals as they grow and evolve. The JCSG will continue to develop new technologies and methodologies, both experimental and computational, to address the spectrum of targets that will be presented, while keeping cost per structure to a minimum and quality to the highest standard. Integration within the PSI Network will be a high priority to embrace interactions with the Biology Partnership centers, future PARS, and the community, as well as support for all PSI Network activities, including the PSI-SGKB and PSI-MR. The JCSG will capitalize on its extensive experience to develop the best strategies to enhance chances of success and eliminate those that lead to failure. Contribution to the original PSI mission of extending structural coverage of the expanding protein universe will be advanced through judicious choice of targets, as will development of tools and collaborations that facilitate dissection of entire networks, pathways and molecular machineries for single organisms or cells from a structural perspective. The biomedical theme project will focus on the human microbiome. Interactions of commensal bacteria with the human body are profound and have a significant impact on maintenance of general human health, but are also associated with obesity, inflammatory diseases, diabetes and certain cancers to name but a few. The JCSG will leverage its HT platform to promote the biological and biomedical impact of all of its structures through extensive biophysical, functional and bioinformatics analyses in collaboration with the other PSI:Biology participants. Thus, the overall goal is to provide a robust, flexible HT structure determination platform that will meet the challenges and embrace the new opportunities that arise from the projects emanating from the PSI:Biology Partnerships and other PSI-supported projects. Furthermore, we will strive along with the PSI Network to promote widespread use of the PSI resources, materials, methodologies, data and models to the general scientific community. PUBLIC HEALTH RELEVANCE: Many of the targets have direct relevance to human disease. Commensal bacteria in the human gut provide tremendous metabolic benefits, but perturbation of the symbiotic balance is linked to obesity, cancer, and inflammatory and other diseases. Structural and biological studies of proteins from the human microbiome (gut and other) and other biomedically important PSI:Biology targets will provide invaluable insights into their function and enhance discovery of new therapeutics and treatments for disease.